Medicine and Health Sciences Commons^™

Mitochondrial Membrane Permeability Inhibitors In Acute Myocardial Infarction Still Awaiting Translation, Cory Trankle, Clinton J. Thurber, Stefano Toldo, Antonio Abbate

Internal Medicine Publications

Despite therapeutic advances, acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. One potential limitation of the current treatment paradigm is the lack of effective therapies to optimize reperfusion after ischemia and prevent reperfusion-mediated injury. Experimental studies indicate that this process accounts for up to 50% of the final infarct size, lending it importance as a potential target for cardioprotection. However, multiple therapeutic approaches have shown potential in pre-clinical and early phase trials but a paucity of clear clinical benefit when expanded to larger studies. Here we explore this history of trials and errors of the …

Donor Ifnl4 Genotype Is Associated With Early Post-Transplant Fibrosis In Recipients With Hepatitis C, Taylor Aiken, Ari Garber, Dawn Thomas, Nicole Hamon, Rocio Lopez, Rajesh Konjeti, Arthur Mccullough, Nizar Zein, John Fung, Medhat Askar, Binu V. John

Internal Medicine Publications

Background and Aims

Early post-transplant hepatic fibrosis is associated with poor outcomes and may be influenced by donor/recipient genetic factors. The rs368234815 IFNL4 polymorphism is related to the previously described IL28B polymorphism, which predicts etiology-independent hepatic fibrosis. The aim of this study was to identify the impact of donor and/or recipient IFNL4 genotype on early fibrosis among patients transplanted for hepatitis C (HCV).

Methods

Clinical data were collected for 302 consecutive patients transplanted for HCV. 116 patients who had available liver biopsies and donor/recipient DNA were included. 28% of these patients with stage 2 fibrosis or greater were compared to …

Increased Pleiotrophin Concentrations In Papillary Thyroid Cancer, Youn Hee Jee, Samira M. Sadowsk, Francesco S. Celi, Liqiang Xi, Mark Raffeld, David B. Sacks, Alan T. Remaley, Anton Wellstein, Electron Kebebew, Jeffrey Baron

Internal Medicine Publications

Background Thyroid nodules are common, and approximately 5% of these nodules are malignant. Pleiotrophin (PTN) is a heparin-binding growth factor which is overexpressed in many cancers. The expression of PTN in papillary thyroid cancer (PTC) is unknown. Method and Findings 74 subjects (age 47 ± 12 y, 15 males) who had thyroidectomy with a histological diagnosis: 79 benign nodules and 23 PTCs (10 classic, 6 tall cell, 6 follicular variant and 1 undetermined). Fine-needle aspiration (FNA) samples were obtained ex vivo from surgically excised tissue and assayed for PTN and thyroglobulin (Tg). Immunohistochemistry (IHC) was performed on tissue sections. In …

Infant Hand Preference And The Development Of Cognitive Abilities, George F. Michel, Julie M. Campbell, Emily C. Marcinowski, Eliza L. Nelson, Iryna Babik

Physical Therapy Publications

Hand preference develops in the first two postnatal years with nearly half of infants exhibiting a consistent early preference for acquiring objects. Others exhibit a more variable developmental trajectory but by the end of their second postnatal year, most exhibit a consistent hand preference for role-differentiated bimanual manipulation. According to some forms of embodiment theory, these differences in hand use patterns should influence the way children interact with their environments, which, in turn, should affect the structure and function of brain development. Such early differences in brain development should result in different trajectories of psychological development. We present evidence that …

Burden And Depression Among Caregivers Of Visually Impaired Patients In A Canadian Population, Zainab Khan, Puneet S. Braich, Karim Rahim, Jaspreet S. Rayat, Lin Xing, Munir Iqbal, Karim Mohamed Mohamed, Sanjay Sharma, David Almeida

Ophthalmology Publications

Purpose/Background. This study reports the degree of burden and the proportion at risk for depression among individuals who provide care to visually impaired patients. Study Design. This is clinic-based, cross-sectional survey in a tertiary care hospital. Methods. Caregivers were considered unpaid family members for patients whose sole impairment was visual. Patients were stratified by vision in their better seeing eye into two groups: Group 1 had visual acuity between 6/18 and 6/60 and Group 2 were those who had 6/60 or worse. Burden was evaluated by the Burden Index of Caregivers and the prevalence of being at …

Burden And Depression Among Caregivers Of Visually Impaired Patients In A Canadian Population, Zainab Khan, Puneet S. Braich, Karim Rahim, Jaspreet S. Rayat, Lin Xing, Munir Iqbal, Karim Mohamed, Sanjay Sharma, David Almeida

Ophthalmology Publications

Purpose/Background. This study reports the degree of burden and the proportion at risk for depression among individuals who provide care to visually impaired patients. Study Design. This is clinic-based, cross-sectional survey in a tertiary care hospital. Methods. Caregivers were considered unpaid family members for patients whose sole impairment was visual. Patients were stratified by vision in their better seeing eye into two groups: Group 1 had visual acuity between 6/18 and 6/60 and Group 2 were those who had 6/60 or worse. Burden was evaluated by the Burden Index of Caregivers and the prevalence of being at risk for depression …

Role Of The Calcium Plateau In The Neuronal Injury And Behavioral Morbidities Following Organophosphate Intoxication, Laxmikant S. Deshpande, Robert E. Blair, Kristin F. Phillips, Robert J. Delorenzo

Neurology Publications

Organophosphate (OP) chemicals include nerve agents and pesticides, and there is a growing concern of OP based chemical attacks against civilians. Current antidotes are essential in limiting immediate mortality associated with OP exposure. However, further research is needed to identify molecular mechanisms underlying long-term neurological deficits following survival of OP toxicity in order to develop effective therapeutics. We have developed rat survival models of OP induced status epilepticus (SE) that mimic chronic mortality and morbidity following OP intoxication. We have observed significant elevations in hippocampal calcium levels after OP SE that persisted for weeks following initial survival. Drugs inhibiting intracellular …

Cannabinoid Receptor Interacting Protein Suppresses Agonist-Driven Cb1 Receptor Internalization And Regulates Receptor Replenishment In An Agonist-Biased Manner, Lawrence C. Blumes, Sandra Leone-Kabler, Deborah J. Luessen, Glenn S. Marrs, Erica Lyons, Caroline E. Bass, Rong Chen, Dana E. Selley, Allyn C. Howlett

Neurology Publications

Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1R) distal C-terminus-associated protein that modulates CB1R signaling via G proteins, and CB1R down-regulation but not desensitization (Blume et al. [2015] Cell Signal., 27, 716-726; Smith et al. [2015] Mol. Pharmacol., 87, 747-765). In this study, we determined the involvement of CRIP1a in CB1R plasma membrane trafficking. To follow the effects of agonists and antagonists on cell surface CB(1)Rs, we utilized the genetically homogeneous cloned neuronal cell line N18TG2, which endogenously expresses both CB1R and CRIP1a, and exhibits a well-characterized endocannabinoid signaling system. We developed stable CRIP1a-over-expressing and CRIP1a-siRNA-silenced knockdown …

Projecting Productivity Losses For Cancer-Related Mortality 2011 – 2030, Alison Pearce, Cathy Bradley, Paul Hanly, Ciaran O’Neill, Audrey Alforque Thomas, Michal Molcho, Linda Sharp

Emergency Medicine Publications

Background

When individuals stop working due to cancer this represents a loss to society – the loss of productivity. The aim of this analysis was to estimate productivity losses associated with premature mortality from all adult cancers and from the 20 highest mortality adult cancers in Ireland in 2011, and project these losses until 2030.

Methods

An incidence-based method was used to estimate the cost of cancer deaths between 2011 and 2030 using the Human Capital Approach. National data were used for cancer, population and economic inputs. Both paid work and unpaid household activities were included. Sensitivity analyses estimated the …

Sirt1 Expression Is Associated With Cd31 Expression In Blood Cells From Patients With Chronic Obstructive Pulmonary Disease, Ryo Kato, Shiro Mizuno, Maiko Kadowaki, Kohei Shiozaki, Masaya Akai, Ken Nakagawa, Taku Oikawa, Masaharu Iguchi, Kazuhiro Osanai, Takeshi Ishizaki, Norbert F. Voelkel, Hirohisa Toga

Emergency Medicine Publications

Background: Cigarette smoke induced oxidative stress has been shown to reduce silent information regulator 1 (Sirt1) levels in lung tissue from smokers and patients with COPD patients. Sirt1 is known to inhibit endothelial senescence and may play a protective role in vascular cells. Endothelial progenitor cells (EPCs) are mobilized into circulation under various pathophysiological conditions, and are thought to play an important role in tissue repair in chronic obstructive lung disease (COPD). Therefore, Sirt1 and EPC-associated mRNAs were measured in blood samples from patients with COPD and from cultured CD34+ progenitor cells to examine whether these genes are associated with …

What Are The Needs Of Older Adults?, Edward F. Ansello

Director's Editorials from Age in Action

Mobility, social connections, health declines, lifelong learning, safety, caretakers or caregivers speak to interdependence or assisted autonomy, rather than to independence. Realizing the best of ourselves means that we are engaged or interdependent with others.

Animal Cruelty And Elder Abuse, Edward F. Ansello

Director's Editorials from Age in Action

Continuing and expanding the American Psychological Association's guidance that those in counseling roles be alert to and ask questions about care of animals could provide some early warnings, perhaps in time to avoid harm to both animals and people. Encouraging our children to interact with kindness towards animals can’t help but pay dividends over the life course. We need to pay attention to the link of indifference or neglect of pets leading to the same with humans, with those in later life.

Fix And Fit To Age In Place, Edward F. Ansello

Director's Editorials from Age in Action

If aging in place is the goal, simple targeted improvements to one’s home and ability to function in it may be central.

Neighborhood Walkability And Health, Edward F. Ansello

Director's Editorials from Age in Action

The apparent benefit of neighborhood walkability suggests that it may be an important health-related consideration in the lives of everyday people. Most of the elements in the walkability index reflect components in the environment, so these may be relevant across the continuum of impairments, meaning that walkable neighborhoods themselves may have positive impact on the daily lives of people with physical or intellectual disabilities.

Palliative Care Is More Care, Not Less, Rachel Selby-Penczak

Case Studies from Age in Action

Educational Objectives:

1. Discuss the origins of hospice and palliative care.

2. Compare and contrast Curative, Palliative, and Hospice Models of Care.

3. Identify when palliative care is appropriate.

Palette: An Intergenerational Art Program To Improve Health Care Delivery And Health Outcomes Of Older Adults, Sadie Rubin

Case Studies from Age in Action

Educational Objectives:

1. Demonstrate the positive out-comes of the PALETTE model in training and educating health pro-fessional students in gerontological experiences.

2. Describe the partnerships devel-oped and their importance in exe-cuting PALETTE programs.

3. Highlight student experiences in intergenerational visual arts and intergenerational movement arts.

Evaluating Commonwealth Coordinated Care: The Experiences Of Individuals Dually Eligible For Medicare And Medicaid, Gerald Craver, Alison Cuellar, Gilbert Gimm

Case Studies from Age in Action

Objectives

1. To understand Virginia’s rationale for implementing the Commonwealth Coordinated Care Program and its approach to evaluating it.

2. To provide a framework for examining the health care experiences of individuals with behavioral health and/or long-term service and support needs who are enrolled in the Commonwealth Coordinated Care Program.

3. To inform policy on future options for improving the quality and health care experiences of similar groups of individuals in Virginia and other states.

Averting Financial Exploitation And Undue Influence Through Legislation, Kathy Pryor

Case Studies from Age in Action

Objectives

1. Explain what financial exploitation is.

2. Examine the elements of undue influence through case studies.

3. Consider the reasons undue influence is so difficult to address legislatively.

New Platinum Agents, Triplatin And Triplatin Nc, Suppress Advanced Breast And Pancreatic Cancer, Stephanie C. Demasi, Kazuaki Takabe Md, Ph.D., Facs

MD Student Summer Research Fellowship Program Posters

• Triplatin and Triplatin NC suppressed cell growth of both Breast Cancer and Pancreatic Cancer in a dose dependent manner in vitro.

• Both Triplatin and TriplatinNC demonstrated growth suppression of the primary breast tumor. A single animal (in the TriplatinNCgroup) was sacrificed due to weight loss.

• In the advanced ex vivo lung metastasis model our most striking results were observed, where the agents nearly prohibited lung metastasis from occurring.

• In the pancreatic cancer peritoneal carcinomatosis model, Triplatin reduced total tumor burden. Mouse survival was significantlyenhanced by the Triplatin treatment group and no mouse developed weight loss more …

Retrospective Review Of Intra-Articular Hip Steroid Injections And Their Association With Rapidly-Progressive Osteoarthritis, Christopher Bednarz, Robert O'Connell Md, Gregory Golladay Md, William Jiranek Md

MD Student Summer Research Fellowship Program Posters

Based on strict inclusion criteria, 109 patients were eligible for analysis in this study. Of these patients, 23 developed RPOA—representing an incidence of 21%.

The characteristics of patients who went on to develop RPOA in this study were: worse initial Kellgren-Lawrence grade and older age.

Future studies of larger sample size that also include outcomes of patients who did not receive intra-articular injections will be needed to establish a causal relationship between these injections and RPOA.

Sestrin2 Is Induced By Glucose Starvation Via The Unfolded Protein Response And Protects Cells From Non-Canonical Necroptotic Cell Death, Boxiao Ding, Anita Parmigiani, Ajit S. Divakaruni, Kellie Archer, Anne N. Murphy, Andrei V. Budanov

Human and Molecular Genetics Publications

Sestrin2 is a member of a family of stress responsive proteins, which controls cell viability via antioxidant activity and regulation of the mammalian target of rapamycin protein kinase (mTOR). Sestrin2 is induced by different stress insults, which diminish ATP production and induce energetic stress in the cells. Glucose is a critical substrate for ATP production utilized via glycolysis and mitochondrial respiration as well as for glycosylation of newly synthesized proteins in the endoplasmic reticulum (ER) and Golgi. Thus, glucose starvation causes both energy deficiency and activation of ER stress followed by the unfolding protein response (UPR). Here, we show that …

Rnaseq Analyses Identify Tumor Necrosis Factor-Mediated Inflammation As A Major Abnormality In Als Spinal Cord, David G. Brohawn, Laura C. O'Brien, James P. Bennett

Human and Molecular Genetics Publications

ALS is a rapidly progressive, devastating neurodegenerative illness of adults that produces disabling weakness and spasticity arising from death of lower and upper motor neurons. No meaningful therapies exist to slow ALS progression, and molecular insights into pathogenesis and progression are sorely needed. In that context, we used high-depth, next generation RNA sequencing (RNAseq, Illumina) to define gene network abnormalities in RNA samples depleted of rRNA and isolated from cervical spinal cord sections of 7 ALS and 8 CTL samples. We aligned >50 million 2X150 bp paired-end sequences/sample to the hg19 human genome and applied three different algorithms (Cuffdiff2 …

Krüppel-Like Transcription Factor Klf1 Is Required For Optimal Γ- And Β-Globin Expression In Human Fetal Erythroblasts, Divya Vinjamur, Yousef N. Alhashem, Safa Mohamad, Parth Amin, David C. Williams Jr., Joyce A. Lloyd

Human and Molecular Genetics Publications

In human adult erythroid cells, lower than normal levels of Krüppel-like transcription factor 1 (KLF1) are generally associated with decreased adult β- and increased fetal γ-globin gene expression. KLF1 also regulates BCL11A, a known repressor of adult γ-globin expression. In seeming contrast to the findings in adult cells, lower amounts of KLF1 correlate with both reduced embryonic and reduced fetal β-like globin mRNA in mouse embryonic erythroid cells. The role of KLF1 in primary human fetal erythroid cells, which express both γ- and β-globin mRNA, is less well understood. Therefore, we studied the role of KLF1 in ex vivo differentiated …

Postpartum Visit Attendance Increases The Use Of Modern Contraceptives, Saba W. Masho, Susan Cha, Rashel Charles, Elizabeth Mcgee, Nicole Karjane, Linda Hines, Susan G. Kornstein

Family Medicine and Population Health Publications

Background. Delays in postpartum contraceptive use may increase risk for unintended or rapid repeat pregnancies. The postpartum care visit (PPCV) is a good opportunity for women to discuss family planning options with their health care providers. This study examined the association between PPCV attendance and modern contraceptive use using data from a managed care organization. Methods. Claims and demographic and administrative data came from a nonprofit managed care organization in Virginia (2008–2012). Information on the most recent delivery for mothers with singleton births was analyzed (N = 24,619). Routine PPCV (yes, no) and modern contraceptive use were both dichotomized. Descriptive …

Loneliness, Depression, And Inflammation: Evidence From The Multi-Ethnic Study Of Atherosclerosis, Briana Mezuk, Moon Choi, Amy S. Desantis, Stephen R. Rapp, Ana V. Diez Roux, Teresa Seeman

Family Medicine and Population Health Publications

Objective

Both objective and subjective aspects of social isolation have been associated with alterations in immune markers relevant to multiple chronic diseases among older adults. However, these associations may be confounded by health status, and it is unclear whether these social factors are associated with immune functioning among relatively healthy adults. The goal of this study was to examine the associations between perceived loneliness and circulating levels of inflammatory markers among a diverse sample of adults.

Methods

Data come from a subset of the Multi-Ethnic Study of Atherosclerosis (n = 441). Loneliness was measured by three items derived from the …

Association Between High School Students’ Cigarette Smoking, Asthma And Related Beliefs: A Population-Based Study, Resa M. Jones, Kara P. Wiseman, Marina Kharitonova

Family Medicine and Population Health Publications

Background

Smoking has a detrimental effect on the symptoms and severity of asthma, a common chronic disease among adolescents. The purpose of this study was to examine the association between asthma and smoking among high school students and assess provider-patient communication with asthmatic adolescents regarding smoking and adolescents’ beliefs about the harms of smoking.

Methods

In fall 2014, data from high school students, ages 14–18 years, completing the 2009-2010 Virginia Youth Tobacco Survey (N = 1796) were used in descriptive analyses and multivariable logistic regression models adjusting for model-specific confounders as appropriate.

Results

Overall, an estimated 19 % of …

Sex And Gender In Medical Education, And Proceedings From The 2015 Sex And Gender Education Summit, Eliza L. Chin, Marley Hoggatt, Alyson J. Mcgregor, Mary K. Rojek, Kimberly Templeton, Robert Casanova, Wendy S. Klein, Virginia M. Miller, Marjorie Jenkins

Family Medicine and Population Health Publications

The Sex and Gender Medical Education Summit: a roadmap for curricular innovation was a collaborative initiative of the American Medical Women's Association, Laura W. Bush Institute for Women’s Health, Mayo Clinic, and Society for Women's Health Research (www.sgbmeducationsummit.com). It was held on October 18–19, 2015 to provide a unique venue for collaboration among nationally and internationally renowned experts in developing a roadmap for the incorporation of sex and gender based concepts into medical education curricula. The Summit engaged 148 in-person attendees for the 1 1/2-day program. Pre- and post-Summit surveys assessed the impact of the Summit, and workshop discussions provided …

Pre-Pregnancy Obesity And Non-Adherence To Multivitamin Use: Findings From The National Pregnancy Risk Assessment Monitoring System (2009–2011), Saba W. Masho, Amani Bassyouni, Susan Cha

Family Medicine and Population Health Publications

Background

Although adequate folic acid or multivitamins can prevent up to 70 % of neural tube defects, the majority of U.S. non-pregnant women of childbearing age do not use multivitamins every day. Factors influencing consistent multivitamin use are not fully explored. This study aims to investigate the association between pre-pregnancy body mass index (BMI) and multivitamin use before pregnancy using a large, nationally representative sample of women with recent live births.

Methods

The national 2009–2011 Pregnancy Risk Assessment Monitoring System data were analyzed. The sample included women with recent singleton live births (N = 104,211). The outcome of interest …

The Pathogen-Occupied Vacuoles Of Anaplasma Phagocytophilum And Anaplasma Marginale Interact With The Endoplasmic Reticulum, Hilary K. Truchan, Chelsea L. Cockburn, Kathryn S. Hebert, Forgivemore Magunda, Susan M. Noh, Jason A. Carlyon

Microbiology and Immunology Publications

The genus Anaplasma consists of tick-transmitted obligate intracellular bacteria that invade white or red blood cells to cause debilitating and potentially fatal infections. A. phagocytophilum, a human and veterinary pathogen, infects neutrophils to cause granulocytic anaplasmosis. A. marginale invades bovine erythrocytes. Evidence suggests that both species may also infect endothelial cells in vivo. In mammalian and arthropod host cells, A. phagocytophilum and A. marginale reside in host cell derived pathogen-occupied vacuoles (POVs). While it was recently demonstrated that the A. phagocytophilum-occupied vacuole (ApV) intercepts membrane traffic from the trans-Golgi network, it is unclear if it or …

Involvement Of Nadh Oxidase In Biofilm Formation In Streptococcus Sanguinis, Xiuchun Ge, Xiaoli Shi, Limei Shi, Jinlin Liu, Victoria Stone, Fanxiang Kong, Todd Kitten, Ping Xu

Microbiology and Immunology Publications

Biofilms play important roles in microbial communities and are related to infectious diseases. Here, we report direct evidence that a bacterial nox gene encoding NADH oxidase is involved in biofilm formation. A dramatic reduction in biofilm formation was observed in a Streptococcus sanguinis nox mutant under anaerobic conditions without any decrease in growth. The membrane fluidity of the mutant bacterial cells was found to be decreased and the fatty acid composition altered, with increased palmitic acid and decreased stearic acid and vaccenic acid. Extracellular DNA of the mutant was reduced in abundance and bacterial competence was suppressed. Gene expression analysis …